1. Field of the Invention
Vaccination against both bacterial and viral diseases has been one of the major accomplishments of medicine over the past century. While effective vaccines have been developed for a large number of diseases, development of safe and effective vaccines for a number of other diseases remains problematic. The use of killed microbial agents as a vaccine, although generally safe, will not always be effective if the immunogenic characteristics of the agent are altered. In contrast, the preparation of live, attenuated microbial agents as a vaccine will often provide improved immunologic reactivity, but increases the risk that the vaccine itself will be infectious, e.g., as a result of reversion, and that the organism will be able to propagate and provide a reservoir for future infection. Thus, although much experience has been gained over the years relating to the preparation of bacterial and viral vaccines, the successful preparation of an effective vaccine against a particular infectious agent can never be assured, even when employing techniques which have been successful for other infectious microorganisms.
Vesicular stomatitis is an acute viral disease which is most prevalent in cattle, but which also affects horses, swine and even human beings. Although not generally fatal, the disease can cause substantial economic loss in cattle as a result of diminished milk production in dairy cattle, weight loss in beef cattle, and the like. For that reason, it would be desirable to provide a safe and effective vaccine against vesicular stomatitis for cattle and other susceptible mammalian hosts.
2. Description of the Prior Art
Modified live vesicular stomatitis virus (VSV) vaccines have been developed. See, e.g., Castaneda et al. (1977) Develop. Biol. Standards 35:429-436; Lauerman et al. (1962) Proc. U.S. Livestock San. Assoc. 66:365-369; and Lauerman and Hanson (1963) Proc. U.S. Livestock San. Assoc. 67:483-490. Inactivated VSV vaccines have been developed. See, e.g., Correa (1964) Am. J. Vet. Res. 25:1300-1302; Holbrook and Geleta (1957) Proc. U.S. Livestock San. Assoc. 61:308-815; and Brown et al. (1966) J. Immunol. 96:537-545. None of these modified live or inactivated viral vaccines have been entirely satisfactory.
Isaacs et al. (1977) Biochemistry 16:1058-1064, describe the synthesis of several psoralen derivatives and their photoreactivity with double-standard RNA. Hanson et al. (1978) J. Gen. Virol. 40:345-358 describe the photoreactivity of various psoralen derivatives with animal viruses. Hanson, in Medical Virology II, Proceedings of the 1982 International Symposium on Medical Virology, de la Maza and Peterson, ed., New York, Elsevier Biomedical, 1983, pp. 45-75, has cited unpublished data on the inactivation of Bluetongue virus utilizing psoralen photochemistry.
The reactivity of psoralen derivatives with VSV was studied by Hearst and Thiry (1977) Nuc. Acids Res. 4:1339-1347 and Talib and Banerjee (1982) Virology 118:430-438, although neither reference disclosed the preparation or use of psoralen-inactivated VSV vaccines. The preparation and use of other psoralen inactivated viral vaccines are described in copending application Ser. No. 563,939, filed on Dec. 20, 1983.